Investing.com -- Shares of Leap Therapeutics (NASDAQ:LPTX) tumbled 64% in pre-open trading Tuesday as the company announced that its DisTinGuish study of sirexatamab combined with tislelizumab and chemotherapy did not meet the primary progression-free survival (PFS) endpoints for patients with advanced gastric cancer. The disappointing outcome has led the company to halt plans for Phase 3 studies in this indication.
Leap Therapeutics reported that while the study showed some activity in biomarker populations, it failed to produce a decisive positive signal. The study's data suggested a high level of discordance between investigator assessment and Blinded Independent (LON:IOG) Central Review, complicating the results. Consequently, Leap Therapeutics has decided to redirect its efforts and resources towards advancing sirexatamab in colorectal cancer (CRC) and to seek strategic partnerships for its development in gastric cancer and other DKK1-high indications.
The study, which enrolled 170 first-line, HER2-negative patients with advanced gastroesophageal junction (GEJ) and gastric cancer, compared the efficacy of sirexatamab in combination with tislelizumab and chemotherapy against tislelizumab and chemotherapy alone. Despite the setback, the company highlighted that the combination treatment was well tolerated and did not add toxicity beyond the standard care.
In the intent-to-treat (ITT (NYSE:ITT)) population, the experimental arm showed a confirmed objective response rate (ORR) of 52%, which was comparable to the control arm's ORR by investigator assessment. However, the preliminary median PFS was shorter in the experimental arm compared to the control arm, both by independent review and investigator assessment.
For patients with DKK1-high tumors, the experimental arm demonstrated a confirmed ORR of 59%, outperforming the control arm's 36%. Yet, the preliminary median PFS did not show a significant advantage for the experimental arm, with a hazard ratio indicating only a trend favoring the experimental arm over the control.
Leap Therapeutics' decision to not proceed with Phase 3 studies in gastric cancer reflects the challenges in achieving clear efficacy signals in this complex tumor type. The company's strategic shift to CRC and the pursuit of partnerships indicates a recalibration of its development priorities in light of the recent study outcomes.
Despite the set back in advanced gastric cancer, the company announced positive initial data from Part B of the DeFianCe study evaluating sirexatamab (DKN-01) in combination with bevacizumab and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC).
"Data from Part B of the DeFianCe study closely mirror the findings from Part A, and together they demonstrate the potential of sirexatamab to provide a compelling treatment option for second-line CRC patients who do not benefit from current standard of care," said Cynthia Sirard, M.D., Chief Medical (TASE:PMCN) Officer of Leap. "Along with consistently achieving higher response rates than the control arm, the data also point to a favorable safety profile. While not yet fully mature, we are encouraged by the progression-free survival data thus far across key subgroups in the study. We look forward to reporting additional data from Part B as it matures over the coming months and beginning our planning for Phase 3 registrational studies."
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